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dc.contributor.authorCano-Ochando, Jordi 
dc.contributor.authorFayad, Zahi A
dc.contributor.authorMadsen, Joren C
dc.contributor.authorNetea, Mihai G
dc.contributor.authorMulder, Willem J M
dc.identifier.citationAm J Transplant. 2020 Jan;20(1):10-18.es_ES
dc.description.abstractConsistent induction of donor-specific unresponsiveness in the absence of continuous immunosuppressive therapy and toxic effects remains a difficult task in clinical organ transplantation. Transplant immunologists have developed numerous experimental treatments that target antigen-presentation (signal 1), costimulation (signal 2), and cytokine production (signal 3) to establish transplantation tolerance. While promising results have been obtained using therapeutic approaches that predominantly target the adaptive immune response, the long-term graft survival rates remain suboptimal. This suggests the existence of unrecognized allograft rejection mechanisms that contribute to organ failure. We postulate that trained immunity stimulatory pathways are critical to the immune response that mediates graft loss. Trained immunity is a recently discovered functional program of the innate immune system, which is characterized by nonpermanent epigenetic and metabolic reprogramming of macrophages. Since trained macrophages upregulate costimulatory molecules (signal 2) and produce pro-inflammatory cytokines (signal 3), they contribute to potent graft reactive immune responses and organ transplant rejection. In this review, we summarize the detrimental effects of trained immunity in the context of organ transplantation and describe pathways that induce macrophage training associated with graft rejection.es_ES
dc.description.sponsorshipThe authors’ work is supported by National Institutes of Health grants R01 AI139623AI (JO); R01 CA220234, R01 HL144072, P01 HL131478, and Netherlands Organization for Scientific Research (NWO) grant ZonMW Vici 91818622 (WJMM); R01 HL143814 and P01HL131478 (ZAF); European Research Council (ERC) Consolidator Grant (310372) and Spinoza Grant of the Netherlands Organization for Scientific Research (MGN); and UO1 AI131470 (JCM).es_ES
dc.publisherWiley es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshGraft Rejection es_ES
dc.subject.meshHumans es_ES
dc.subject.meshImmune Tolerance es_ES
dc.subject.meshImmunity, Innate es_ES
dc.subject.meshMacrophages es_ES
dc.subject.meshOrgan Transplantation es_ES
dc.subject.meshTransplantation Immunology es_ES
dc.subject.meshTransplantation Tolerance es_ES
dc.titleTrained immunity in organ transplantation.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial 4.0 Internacional*
dc.contributor.funderNational Institutes of Health (Estados Unidos) 
dc.contributor.funderDutch Research Council (Holanda) 
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.identifier.journalAmerican journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeonses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución-NoComercial 4.0 Internacional
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